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Biomedical subjects

M V Cohen

Publications and source records attributed to M V Cohen.

At least 109 records · Page 6Linked to original sources
PubMed1992

Using contrast material-enhanced echocardiography to identify abnormal pulmonary arteriovenous connections in patients with hypoxemia.

The phenomenon of abnormal pulmonary arteriovenous connections in patients with acquired lung disease rarely has been reported. We report three patients with acquired lung disease and hypoxia that did not respond to the administration of 100 percent oxygen. Contrast-material-enhanced echocardiography demonstrated intrapulmonary right-to-left shunting in all three patients. These cases suggest that patients with hypoxia due to acquired lung disease may be screened by contrast-enhanced echocardiography to identify the presence and the location of anatomic right-to-left shunts.

Aged↗
PubMed1991

Ventricular fibrillation threshold is influenced by left ventricular stretch and mass in the absence of ischaemia.

STUDY OBJECTIVE: Ischaemic heart disease is known to contribute to the development of ventricular arrhythmias. However, the role of non-ischaemic variables has been less well defined. We therefore studied the effect of myocardial stretch and ventricular mass on the vulnerability of the rat heart to ventricular fibrillation. DESIGN AND EXPERIMENTAL MATERIAL: Two groups of rat hearts were studied in an isolated buffer perfused apparatus: group I, mature female animals with an average dry left ventricular weight of 73 mg and group II, a group of retired breeders with an average left ventricular weight of 122 mg. Hearts performed isovolumetric work at either low (0 mm Hg) or high (20 mm Hg) left ventricular end diastolic pressures. MEASUREMENTS AND MAIN RESULTS: Ventricular fibrillation was provoked by trains of ventricular extrastimuli delivered at increasing current until development of the arrhythmia. The current required to provoke ventricular fibrillation decreased in both groups at the high left ventricular end diastolic pressure and the larger hearts in group II were more vulnerable to ventricular fibrillation than those in group I. The decrease in ventricular fibrillation threshold occurred in the absence of an increase in myocardial lactate production or a decrease in endocardial to epicardial flow ratios. CONCLUSIONS: This study thus identified two variables, myocardial stretch and ventricular mass, which influence the development of ventricular fibrillation and which are independent of myocardial ischaemia in this animal model. These observations may be relevant to an understanding of the increased incidence of lethal arrhythmias which occur in patients with dilated cardiomyopathies.

Animals↗
PubMed1991

Low rate of treatment of hypercholesterolemia by cardiologists in patients with suspected and proven coronary artery disease.

BACKGROUND: Although specific guidelines for the treatment of hypercholesterolemia have been published, it is not known whether physicians treating patients likely to have lipid disorders have adopted the recommendations. METHODS AND RESULTS: The approach of cardiologists to the treatment of hypercholesterolemia in a metropolitan teaching hospital was assessed by interviewing patients with chest pain who were admitted for coronary angiography in 1988-1989 and by measuring fasting blood lipid profiles. At 1 month and again 12-24 months later, patients were contacted by telephone to determine if there had been any changes in treatment. Of 95 patients evaluated, 81 had coronary artery disease. Only 17% of those with high levels of total cholesterol and/or low density lipoprotein cholesterol were being actively treated with diet and/or drugs. In the remaining patients, either lipid studies had not been done or abnormal results had not been addressed. There was little change in treatment approach during the month after the diagnostic procedure. Furthermore, the experience was similar in those patients subjected to coronary revascularization. One to 2 years after the initial intervention, 69 of the original study group could be contacted again. Although active dietary or pharmacological therapy was initiated in some individuals during this interval, it was stopped in others. Thirty-five percent of hypercholesterolemic patients were receiving targeted therapy. CONCLUSIONS: Thus, only a small proportion of patients with documented coronary artery disease and hypercholesterolemia were being actively treated for their lipid disorder, suggesting that the published treatment guidelines have not yet been fully accepted. However, an encouraging improvement in frequency of treatment of hypercholesterolemia was documented during the 1-2-year observation period.

Cardiology↗
PubMed1991

Preconditioning causes improved wall motion as well as smaller infarcts after transient coronary occlusion in rabbits.

BACKGROUND: A brief coronary occlusion before a more prolonged occlusion results in less myocardial infarction than the longer occlusion alone. However, the effects of this preconditioning on recovery of systolic function after coronary occlusion have not been determined. METHODS AND RESULTS: Ultrasonic crystals implanted in rabbit myocardium measured segment length in the distribution of a branch of the left coronary artery that was fitted with a snare occluder. Rabbits were randomly allocated to either nonpreconditioned or preconditioned groups. Rabbits in the latter group underwent preconditioning with a 5-minute coronary occlusion followed by 10 minutes of reperfusion. Then the coronary artery was occluded for 20 minutes in all rabbits, after which it was allowed to reperfuse for 90 minutes. The hearts were then excised, and infarct size was measured by staining with triphenyltetrazolium chloride. During coronary occlusion, all hearts except one demonstrated either akinesis or paradoxical bulging. Five minutes after release of the 20-minute occlusion, active shortening had returned in the preconditioned rabbits and averaged 27.9 +/- 16.6% of baseline shortening. At the same time, paradoxical lengthening persisted in nonpreconditioned rabbits (-15.5 +/- 19.8% of baseline). By the end of the 90-minute reperfusion period, segment shortening averaged 40.1 +/- 8.4% of baseline in preconditioned rabbits and only 6.2 +/- 12.0% in nonpreconditioned rabbits (p less than 0.05). Infarct size as a percentage of risk area was significantly smaller in preconditioned rabbits as well (3.0 +/- 1.6% versus 28.8 +/- 7.0%, p less than 0.002) and likely accounted for the improved shortening. CONCLUSIONS: We conclude that a brief coronary occlusion before a more prolonged occlusion results in not only reduced infarct size but also significantly better recovery of systolic function.

Animals↗
PubMed1990

Myocardial stunning in dogs: preconditioning effect and influence of coronary collateral flow.

In open-chest dogs the left anterior descending (LAD) coronary artery diagonal branch was encircled with a pneumatic occluder. Pairs of ultrasonic crystals were inserted into LAD myocardium and remote normal muscle. The coronary artery was occluded for 5 minutes, followed by 10 minutes of reperfusion. This occlusion-reperfusion cycle was repeated 12 times, and after a final 90-minute reperfusion period the hearts were removed and stained with triphenyltetrazolium chloride. No heart had evidence of necrosis. Baseline shortening normalized for end-diastolic length averaged 10.4 +/- 1.0% in the LAD area and 7.4 +/- 0.8% in the remote normal myocardium. When analyzed as a percentage of baseline, segment shortening in the normal myocardium was not significantly altered by LAD occlusion and reperfusion. In contrast, during occlusions the LAD myocardium paradoxically lengthened. With the initial reperfusion, shortening was significantly depressed to 28.6 +/- 8.6% of baseline. Although with subsequent reperfusions the return of function progressively decreased, the rate of deterioration was markedly attenuated after the first occlusion. By the end of the protocol many LAD segments lengthened paradoxically even after reperfusion, but in five hearts in which active contraction was preserved there was no significant change in regional function after the third cycle, suggesting a protective or preconditioning effect of earlier ischemia. There was a moderately good correlation between collateral blood flow and the degree of dysfunction following the initial 10-minute reperfusion (r = -0.73). This correlation deteriorated during subsequent reperfusion periods, implying that collateral blood flow can be a predictor of the extent of myocardial stunning only after the initial one or two reperfusion cycles. Thereafter other as yet unidentified factors make baseline collateral flow unimportant.

Animals↗
PubMed1990

Training in dogs with normal coronary arteries: lack of effect on collateral development.

STUDY OBJECTIVE - The aim of the study was to investigate the effect of exercise training on coronary collateral development in a normal heart animal model. DESIGN - Dogs with normal hearts were fitted with balloon occluders around the left circumflex coronary artery. Haemodynamic variables and myocardial blood flow (using radioactive microspheres) were measured during 1 min circumflex occlusions at rest and during exercise, before and after a 12 week exercise programme. Resting measurements were also made after 4 weeks. SUBJECTS - Trained subjects were 10 one year old beagles; eight beagles served as sedentary controls. Although measurements were made in all dogs at 4 weeks, four trained and three control animals died during the experiment because of complications, so the data reported at 12 weeks are derived from six trained and five sedentary animals. Except during the few occasions when the left circumflex artery was transiently occluded to allow measurement of collateral flow, all coronary arteries were patent and without impediment to normal flow. MEASUREMENTS and RESULTS - Measurements of haemodynamic variables and coronary blood flow were made at the start and repeated at 4 weeks (resting measurements only) and 12 weeks of exercise training. Initial resting circumflex collateral flow was 0.26(SEM 0.05) cm3.g-1.min-1 in the training group and 0.23(0.03) in the control group (NS). The ratio of ischaemic to normal blood flow was 0.16(0.02) in both groups. At 4 weeks there were no changes in either group. At 12 weeks the ischaemic to normal blood flow ratio had increased in both trained and sedentary dogs to 0.24(0.05) and 0.26(0.06) respectively, but the trend over the 12 week period was not significant. The decline in cardiac output and dramatic increase in left atrial pressure during combined coronary occlusion and exercise were comparable in both groups at weeks 1 and 12. CONCLUSIONS - Exercise does not accelerate the development of coronary collaterals in dogs with normal coronary arteries.

Animals↗
PubMed1990

Oxypurinol limits myocardial infarct size in closed chest dogs without pretreatment.

The authors tested whether allopurinol or oxypurinol could limit infarct size when treatment was started just prior to reperfusion and continued until sacrifice. In closed chest, anesthetized dogs, a branch of the left coronary artery was reversibly occluded for 90 mins followed by 24 h of reperfusion. Fifteen minutes prior to reperfusion, dogs received a bolus of either allopurinol (10 dogs), or oxypurinol (nine dogs), 10 mg/kg intravenously, followed by a 24 h infusion, 55 mg/kg/day. Eleven control dogs received equal volumes of saline. Investigators were blinded to the identity of the agent. Hearts were removed 24 h after reperfusion. Arrhythmias for 30 mins after reperfusion were quantitated. Oxypurinol caused 28% less of the risk zone to infarct for any level of collateral flow than that seen in the controls. This difference was significant. Allopurinol-treated hearts averaged only 18% less infarction and did not achieve significance. Ventricular arrhythmias and mortality did not differ among the three groups. Therefore, unlike allopurinol, oxypurinol with continued administration can limit tetrazolium-indicated necrosis in the dog heart in the absence of pretreatment.

Allopurinol↗
PubMed1989

Free radicals in ischemic and reperfusion myocardial injury: is this the time for clinical trials?

An increasing number of studies in cell cultures, isolated perfused hearts, and intact animal preparations purport to show the significance of free radical production in the pathophysiology of myocardial injury and necrosis of ischemic and reoxygenated or reperfused tissue. Additionally an impressive array of therapeutic approaches has been developed to interfere with the generation of free radicals and to thereby salvage jeopardized myocardium. Based on these data clinical trials are now being conducted or planned. However, a critical examination of the experimental data raises questions that undermine total acceptance of the conclusions of the investigators and the enthusiastic extrapolations to the clinical arena. Issues such as endotoxin contamination of infused free radical scavenger enzymes, incorrect dosing, possibly improper selection of control conditions, species specificity, inadequate consideration of the dependence of infarct size on coronary collateral blood flow, and the possibly transient nature of any benefits of anti-free radical interventions cast doubt on some of the accumulated data and their general applicability to humans. These issues must be satisfactorily addressed before this experimental approach can be fully embraced by the clinical cardiologist. Additionally, uniformity in the experimental model and conditions might eliminate some of the confusion and make it easier to compare the results of different studies. Free radical mechanisms may be important in the heart, but more data are needed to rigorously document an unequivocal effect of therapeutic interventions in experimental models before clinical trials are appropriate.

Allopurinol↗
PubMed1989

Chronic whole body sympathectomy fails to protect ischemic rabbit hearts.

We determined whether chronic chemical sympathetic denervation could protect the rabbit heart against ischemia. Rabbits received 10 mg/kg 6-hydroxydopamine (6-HD) twice during the first week, then 100 mg.kg-1.wk-1 for the following 7 wk. After this interval the rabbits were anesthetized, the chests were opened, and in each a coronary branch was occluded for 45 min followed by reperfusion for 3 h. Collateral flow was determined with radioactive microspheres during coronary occlusion. Flow to the ischemic myocardium of the 6-HD group (0.06 +/- 0.03 ml.min-1.g-1) was not significantly different from that in the control group (0.04 +/- 0.02 ml.min-1.g-1). Infarct size was determined with triphenyltetrazolium chloride staining. Average infarct size calculated as a percentage of risk zone was similar in the 6-HD and control groups (59 +/- 15 and 60 +/- 12%, respectively). We conclude that chronic chemical sympathectomy does not induce collateral growth in the rabbit heart. Furthermore, endogenous catecholamines do not contribute to injury in the ischemic rabbit heart.

Animals↗
PubMed1989

Increased myocardial infarct size because of reduced coronary collateral blood flow in beagles.

Effects of permanent left circumflex coronary artery occlusion (CAO) were examined in conscious purebred beagles and mongrel dogs, instrumented with miniature left ventricular (LV) pressure gauges, wall thickness gauges in the ischemic zone, catheters in left atrium and aorta, and snares around the left circumflex coronary artery. Blood flow was measured using the radioactive microsphere technique before CAO and at 5 min, 1, 3, and 24 h after CAO. Although CAO reduced myocardial blood flow similarly in beagles and mongrels, significantly less (P less than 0.05) recovery of myocardial blood flow was observed over the following 24-h period in beagles. Infarct size, as determined by triphenyltetrazolium chloride and expressed as percentage of area at risk, was larger (P less than 0.05) in beagles (62.0 +/- 5.1%) than mongrels (42.5 +/- 4.2%). Thus beagles do not tolerate ischemia as well as mongrel dogs and possess fewer functional coronary collaterals resulting in larger infarcts after CAO.

Animals↗
PubMed1989

Superoxide dismutase reduces reperfusion arrhythmias but fails to salvage regional function or myocardium at risk in conscious dogs.

To determine if oxygen free radical scavengers administered before coronary artery reperfusion can limit reperfusion arrhythmias, increase the return of regional function in ischemic myocardium, and reduce tissue necrosis at 1 week after 90-minute coronary artery occlusion and reperfusion, conscious dogs were treated with superoxide dismutase (SOD) and catalase before and for 1 hour after coronary artery reperfusion. Another group was treated with recombinant SOD (rSOD) because the commercially available SOD and catalase contained endotoxin. The conscious dogs were studied 3-4 weeks after implanting left ventricular pressure gauges, ultrasonic wall thickness gauges in the posterior left ventricular wall, left atrial catheters, and arterial catheters, Doppler flow transducers, and hydraulic occluders on the left circumflex coronary artery. The only beneficial effect observed was that the number of arrhythmic beats per minute in the rSOD-treated group was significantly lower (p less than 0.05) when compared with a control group after coronary artery reperfusion. Treatment neither increased the amount of recovery of wall thickening in the ischemic zone nor reduced infarct size when expressed either as a percentage of the area at risk or as a function of collateral blood flow in the ischemic zone. For example, infarct size as a percentage of the area at risk was 32.6 +/- 5.8%, 37.4 +/- 6.4%, 28.3 +/- 5.1% in the control, SOD and catalase-, and rSOD-treated groups, respectively. Thus, although treatment with oxygen free radical scavengers invoked a transient reduction in the number of reperfusion arrhythmias, this treatment in conscious dogs failed to improve regional myocardial dysfunction or reduce the amount of necrosis when compared with a control group. The lack of a sustained salutary effect may indicate that longer periods of treatment with free radical scavengers are required in chronic preparations.

Animals↗
PubMed1988

Pressure-flow characteristics and nutritional capacity of coronary veins in dogs.

To examine the hemodynamic interdependence of coronary arteries and veins, great cardiac vein (GCV) and left anterior descending (LAD) coronary artery flows of dogs were measured. Although they were not different under base-line conditions, 42.9 +/- 4.1 and 34.9 +/- 5.2 ml/min, respectively, LAD occlusion caused only a 56% decrease in GCV flow, whereas peak GCV flow during reactive hyperemia consistently underestimated peak LAD flow by nearly 40%. The measured hemodynamic data were very closely predicted by a simple model that assumed the presence of a low-resistance venous collateral anastomotic pathway between the GCV and veins outside the LAD territory. The resistance of the venous collaterals averaged 9.9 +/- 3.0% of LAD resistance. Therefore, GCV flow does not solely represent LAD collateral flow when the LAD is occluded, nor is it a reliable indicator of changes in LAD perfusion patterns. Nutritional myocardial perfusion assessed with 133Xe washout decreased from 0.86 +/- 0.16 to 0.13 +/- 0.02 ml.min-1.g-1 after LAD occlusion, whereas retroperfusion of the GCV with arterial blood enhanced washout by 85% to 0.23 +/- 0.03 ml.min-1.g-1 (P less than 0.005). Retroperfusion was inefficient, however, since only 10% of the isotope injected into the GCV gained access to the myocardium.

Animals↗
PubMed1988

Correlation between left ventriculography, auscultation, and M-mode and two-dimensional echocardiography in mitral valve prolapse.

Mitral valve prolapse (MVP) is a common valvular abnormality which is observed in as many as 5% of the general population. Although invasive as well as noninvasive tools have been developed to determine the existence of this disorder, none is perfect and false negative as well as false positive diagnoses abound. Because MVP is a relatively benign disorder, it has also not been easy to make the usual clinical-pathological correlations. Left ventriculography is considered by many to be the gold standard, but this designation is probably not deserved. The angiographic criteria used by most do not permit unequivocal separation of normal mitral valve systolic bulging from pathologic MVP, and the interobserver and intraobserver variability of interpretation is high. However, false positive diagnoses can be eliminated if MVP is diagnosed only when para-annular displacement of mitral leaflet tissue is detected during systole rather than simple leaflet bulging. Although mid-systolic clicks and late systolic murmurs have proven to be the auscultatory hallmarks of this disorder, many patients have these signs without other diagnostic findings, consequently making it impossible to confirm the presence of MVP. Furthermore, the appearance of diagnostic echocardiographic abnormalities in patients with normal cardiac examinations implies that auscultation is not a sensitive marker of MVP. Both M-mode and two-dimensional echocardiography have technical limitations and the repeatability of interpretation of these tests is disappointingly low (80 to 90%). Because of these difficulties the angiographic-echocardiographic correlation is only fair. Nonetheless echocardiography has generally been accepted as the diagnostic modality of choice. Future technical improvements will likely enhance the diagnostic accuracy of this technique.

Echocardiography↗
PubMed1987

Impaired coronary vasodilator responsiveness as a cause of lactate production during pacing-induced ischemia in patients with angina pectoris and normal coronary arteries.

Subgroups of patients with angina pectoris and normal coronary arteries are known to have pacing-induced lactate production and, therefore, myocardial ischemia. To examine the mechanism of this pacing-induced ischemia, the effect of incremental atrial pacing on coronary blood flow and metabolism was studied in 27 patients with angina and normal coronary arteries. Seventeen patients continued to exhibit normal lactate extraction even at heart rates up to 160 beats/min (Group 1), whereas in 10 patients (Group 2) lactate extraction changed to production at the highest pacing rate. Coronary blood flow increased in Group 1 patients by 18, 41 and 75%, respectively, as heart rate was increased by 20 beat/min increments from 100 to 160 beats/min. In contrast, coronary blood flow increased by only 8, 7 and 14%, at the three respective pacing rates in Group 2. Between the heart rates of 100 and 160 beats/min, coronary vascular resistance decreased 32% in Group 1 patients but was unchanged in Group 2 patients. There was no significant change in the ratio of myocardial O2 consumption/rate-pressure product in Group 1 patients, but this ratio decreased from 0.91 +/- 0.26 ml O2 X min-1 X (mm Hg X beats/min)-1 to 0.53 +/- 0.11 (p less than 0.05) in Group 2 patients as heart rate increased from baseline to 160 beats/min. Thus, patients with angina and normal coronary arteries who develop ischemia with pacing have a decreased coronary vasodilator response that interferes with their ability to increase myocardial oxygen supply to match the higher demand.

Adult↗
PubMed1987

Lack of effect of prior training on subsequent ischaemic and infarcting myocardium and collateral development in dogs with normal hearts.

To determine whether exercise training in animals with normal coronary arteries has a salutary effect on ischaemic myocardium, 24 dogs were randomly assigned to be either trained or confined to cages for three months. All dogs then underwent left thoracotomy for placement of indwelling right and left atrial and aortic catheters and a loose snare ligature around the proximal left circumflex coronary artery. Three days after operation control scintigrams were recorded after injection of thallous chloride-201 in animals running on a treadmill to achieve exercise heart rates of 220 beats.min-1. Four days later the snares were pulled to occlude the left circumflex artery and infarct size determined by measuring venous activity of creatine phosphokinase. Three days after infarction the first post-ligation scintigram was performed after thallium-201 injection in exercising animals. Exercise scans were repeated at 10 days and 2, 4, and 6 weeks after coronary ligation. During the final exercise study collateral blood flow was measured with radioactive microspheres. There was no difference in mean creatine phosphokinase appearance time, peak creatine phosphokinase activity, or measured infarct size between the trained and sedentary dogs. The ratio of thallium-201 activity in left circumflex artery or ischaemic area to left anterior descending artery or normally perfused myocardium fell from 100% before occlusion to 86.6% in the sedentary animals and 80.6% in the trained dogs three days after coronary ligation. Although these falls were significant (p less than 0.025 and p less than 0.005 respectively), there was no difference between groups. Over the next five and a half weeks the scintigraphic defect shrank as the thallium-201 ratio gradually increased, but changes were again similar in both groups. At six weeks there was little difference in exercise collateral flow to left circumflex artery myocardium and flow to normal myocardial tissue in cage confined and trained dogs. Therefore, no beneficial effect of exercise training in dogs with normal hearts could be seen on ischaemic or infarcting myocardium or coronary collateral development after coronary ligation.

Animals↗
PubMed1986

Coronary vascular reserve in the greyhound with left ventricular hypertrophy.

The effects of physiological left ventricular hypertrophy on coronary reactivity and reserve were examined by comparing greyhounds with their remarkable myocardial hypertrophy with mongrel dogs (left ventricular body weight ratios 7.7(0.1) and 4.4(0.1) g X kg-1 respectively). Peak reactive hyperaemia and flow debt repayment after 15 s coronary occlusions were virtually identical in both groups at baseline heart rates and paced atrial rates up to 270 beats X min-1. Furthermore, the changes in myocardial blood flow and its transmural distribution after release of a 45 s coronary occlusion both at baseline heart rate and during atrial pacing at 210 beats X min-1 were similar in both greyhounds and mongrel dogs. Collateral flow during a 1 min coronary occlusion in conscious animals and myocardial flows and distribution during treadmill exercise were also similar. To determine minimal coronary vascular resistance intracoronary adenosine (400-600 micrograms X min-1) was infused to dilate maximally the coronary vasculature without having appreciable systemic effects. In both groups of dogs adenosine increased coronary flow six to seven fold. Coronary vascular resistance per gram of left ventricle decreased equally, and the minimal resistance was 2200(147) kPa X litre-1 X min X g (RU X g-1) in greyhounds and 2360(453) RU X g-1 in mongrels, thus indicating similar maximal vascularity in each gram of the hypertrophied and mongrel left ventricles. Because of the larger greyhound heart, the minimal coronary vascular resistance for the entire left ventricle (11.7(0.7)RU) was 50% of that in mongrel dogs (24.1(0.7)RU). Thus all forms of left ventricular hypertrophy cannot be assumed to have similar effects on the coronary vasculature. Whereas the pathological hypertrophy associated with renovascular hypertension and aortic banding is accompanied by decreased coronary vascularity, the myocardial hypertrophy of the greyhound is accompanied by increased total vascularity and preserved coronary reserve.

Adenosine↗